Outcomes of patients with frailty and metastatic cancer admitted to the intensive care unit
Authors: Kosuke Mima, Hideo Baba
Journal: The Lancet Healthy Longevity (2023)

The number of vulnerable older patients with malignancies has increased worldwide.1Ethun CG Bilen MA Jani AB Maithel SK Ogan K Master VA Frailty and cancer: implications for oncology surgery, medical oncology, and radiation oncology.CA Cancer J Clin. 2017; 67: 362-377Crossref PubMed Scopus (326) Google Scholar Frailty is characterised by a progressive decline in physiological reserve and an increased vulnerability to stressors. Accumulating evidence demonstrates that frailty is associated with poor tolerance to treatment, adverse surgical outcomes, and unfavourable survival in patients with critical illness or cancer.2Muscedere J Waters B Varambally A et al.The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis.Intensive Care Med. 2017; 43: 1105-1122Crossref PubMed Scopus (440) Google Scholar, 3Mima K Nakagawa S Miyata T Yamashita YI Baba H Frailty and surgical outcomes in gastrointestinal cancer: integration of geriatric assessment and prehabilitation into surgical practice for vulnerable patients.Ann Gastroenterol Surg. 2023; 7: 27-41Crossref Scopus (4) Google Scholar However, the association between frailty and clinical outcomes in critically ill patients with metastatic cancer remains unclear. In The Lancet Healthy Longevity, Muhammad Alamgeer and colleagues4Alamgeer M Ling RR Ueno R et al.Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort study.Lancet Healthy Longev. 2023; 4: e675-e684Google Scholar have reported the findings from a large registry-based cohort study assessing associations of frailty with clinical outcomes in patients with metastatic cancer admitted to the intensive care unit (ICU). Utilising a database of 21 174 metastatic solid or haematological cancer cases from Australia and New Zealand, Alamgeer and colleagues assessed patient frailty in the 2 months preceding ICU admission according to the clinical frailty scale (CFS), which ranges from 1 (very fit) to 8 (living with very severe frailty). Among the 21 174 patients included in the study, 6806 (32·1%) were frail (CFS score ≥5). Multivariable analyses revealed that frailty was associated with shorter overall survival after ICU admission (adjusted hazard ratio [aHR] 1·52 [95% CI 1·43–1·60, p<0·0001); this prognostic association was observed across various cancer subtypes. Additionally, frailty was associated with shorter survival times in patients younger than 65 years (aHR 1·66 [95% CI 1·51–1·83]) and in patients aged 65 years and older (1·40 [1·38–1·56]) compared with the absence of frailty. However, the effects of frailty on survival time were significantly larger in patients younger than 65 years (pinteraction<0·0001). The management of frail or critically ill patients with metastatic cancer in the ICU is challenging. Time-limited trials of treatments in the ICU have been proposed as one approach to reduce non-beneficial treatments in patients with serious illness.5Vink EE Azoulay E Caplan A Kompanje EJO Bakker J Time-limited trial of intensive care treatment: an overview of current literature.Intensive Care Med. 2018; 44: 1369-1377Crossref PubMed Scopus (92) Google Scholar Alamgeer and colleagues suggest that vulnerable patients with metastatic cancer might benefit from time-limited trials in the ICU. However, several questions remain unanswered. First, the study showed a stronger prognostic association of frailty in patients admitted for elective surgery (aHR 1·85 [95% CI 1·71–2·00]) than in patients admitted for emergency surgery (1·49 [1·34–1·66], pinteraction=0·0010) and medical indications (1.38 [1·29–1·46], pinteraction<0·0001). Therefore, it is necessary to analyse clinical outcomes in the ICU and hospital according to frailty status separately in patients admitted for elective surgery, in patients admitted for emergency surgery, and in patients with medical indications. Second, 32·1% of patients with metastatic cancer had frailty, and nearly 75% of these frail patients survived hospital discharge. However, the association between frailty status and clinical outcomes after ICU discharge in patients with metastatic cancer remains unclear in this study. Taken together, the study findings suggest that frailty might influence surgical outcomes in patients admitted to the ICU following elective surgery, post-ICU treatment (chemotherapy or immunotherapy), and cancer-specific outcomes after ICU discharge in patients with cancer. Hence, future research is required to explore these outcomes according to frailty status in patients with metastatic cancer. There is no consensus on the most appropriate definition of frailty or the most clinically useful tool for assessing frailty in patients with cancer or other severe illnesses. The most commonly used geriatric assessment tools in patients with cancer include the CFS, the Geriatric-8 screening tool, Comprehensive Geriatric Assessment (CGA), and the Kihon checklist (KCL).3Mima K Nakagawa S Miyata T Yamashita YI Baba H Frailty and surgical outcomes in gastrointestinal cancer: integration of geriatric assessment and prehabilitation into surgical practice for vulnerable patients.Ann Gastroenterol Surg. 2023; 7: 27-41Crossref Scopus (4) Google Scholar Retrospective studies evaluating the diagnostic accuracy of these tools suggest that the CFS has low sensitivity (54%), high specificity (100%), and moderate-to-high accuracy for frailty (area under the curve [AUC] 0·77), and that the CGA (84% sensitivity, 86% specificity, and AUC 0·85) and the KCL (90% sensitivity, 81% specificity, and AUC 0·89) might be useful in assessing frailty in patients with cancer.6Kenig J Zychiewicz B Olszewska U Richter P Screening for frailty among older patients with cancer that qualify for abdominal surgery.J Geriatr Oncol. 2015; 6: 52-59Summary Full Text Full Text PDF PubMed Google Scholar, 7Satake S Senda K Hong YJ et al.Validity of the Kihon Checklist for assessing frailty status.Geriatr Gerontol Int. 2016; 16: 709-715Crossref PubMed Google Scholar Although the CFS grading tool is disadvantaged by its semiquantitative classification, higher CFS scores have been associated with poor surgical and survival outcomes in patients with gastrointestinal cancers.8Mima K Miyanari N Morito A et al.Frailty is an independent risk factor for recurrence and mortality following curative resection of stage I-III colorectal cancer.Ann Gastroenterol Surg. 2020; 4: 405-412Crossref PubMed Scopus (0) Google Scholar, 9Mima K Hayashi H Nakagawa S et al.Frailty is associated with poor prognosis after resection for pancreatic cancer.Int J Clin Oncol. 2021; 26: 1938-1946Crossref Scopus (15) Google Scholar The study by Alamgeer and colleagues identified significant correlations between CFS scores and several other frailty indicators, namely older age and a high burden of comorbidities. These findings support the feasibility and use of the CFS in patients with metastatic cancer admitted to the ICU. However, the study found a stronger association between frailty and survival outcomes in patients younger than 65 years, suggesting that geriatric screening tools might not be applicable or appropriate for use in the whole population. Nonetheless, routine collection of geriatric assessment data in future cancer clinical trials is necessary to establish a standardised frailty assessment. There is little evidence of beneficial effects of rehabilitation on critically ill patients or those with cancer.3Mima K Nakagawa S Miyata T Yamashita YI Baba H Frailty and surgical outcomes in gastrointestinal cancer: integration of geriatric assessment and prehabilitation into surgical practice for vulnerable patients.Ann Gastroenterol Surg. 2023; 7: 27-41Crossref Scopus (4) Google Scholar, 10Tipping CJ Harrold M Holland A Romero L Nisbet T Hodgson CL The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review.Intensive Care Med. 2017; 43: 171-183Crossref PubMed Scopus (343) Google Scholar Hence, further studies are required to examine the effects of rehabilitation on functional capacity, clinical outcomes, and quality of life, particularly in frail patients with cancer admitted to the ICU. The study by Alamgeer and colleagues found that frailty was associated with worse short-term and long-term outcomes in patients with metastatic cancer admitted to the ICU. These findings highlight the need to assess frailty for enhanced ICU patient care. We declare no competing interests. Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort studyIn patients with metastatic cancer admitted to the ICU, frailty was associated with poorer long-term survival. Patients with frailty might benefit from a goal-concordant time-limited trial in the ICU and will need suitable post-intensive care supportive management. Full-Text PDF Open Access